Daunorubin 14-hydroxylase

The ability to convert daunorubicin to doxorubicin can be conferred on a host cell by transformation with a recombinant vector comprising DNA encoding daunorubicin 14-hydroxylase. The host cell can then be used to produce doxorubicin.

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Claims

1. A daunorubicin 14-hydroxylase having an amino acid sequence at least 60% identical to the sequence depicted in SEQ ID NO: 2, wherein said daunorubicin 14-hydroxylase has the ability to convert daunorubicin to doxorubicin.

2. The daunorubicin 14-hydroxylase according to claim 1 which has the amino acid sequence of SEQ ID No: 2.

3. The daunorubicin 14-hydroxylase according to claim 1, wherein said amino acid sequence has the same hydrophobicity/hydrophilicity and size as SEQ ID NO: 2.

Referenced Cited
Foreign Patent Documents
WO 97/44439 May 1997 WOX
Other references
  • Dickens et al., Jour. of Bacteriology, vol. 178 No. 11, "Isolation and Characterization of a Gene from Streptomyces sp. Strain C5 That confers the Ability to Convert Daunomycin to Doxorubicin on Streptomyces lividans TK24", pp. 3389-3395, 1996. Columbo et al, Expression of Doxorubicin-Daunorubcin Resistance Genes in Different Anthracycline-producing Muants of Streptomyces peucetius; 1992 J. Bacteriology 174 (5); pp. 1641-1646. Otten et al, Cloning and characterization of the Streptomyces peucetius dnrQS Genes Encoding a Daunosamine Biosynthesis Enzyme and a Glycosyl Transferase Involved in Daunorubicin Biosynthesis; 1995, J. Bacteriol 177 (22); pp. 6668-6692. Otten et al, 1990, Cloning and Expression of Daunorubicin Biosynthesis Genes from Strpetomyces peucetius and S. peucetius subsp. caesius; J. Bacteriol 172 (6); pp. 3427-3434.
Patent History
Patent number: 5786190
Type: Grant
Filed: Dec 3, 1996
Date of Patent: Jul 28, 1998
Assignee: Pharmacia & Upjohn S.p.A. (Milan)
Inventors: Augusto Solari Inventi (Milan), Umberto Breme (Vigevano), Anna Luisa Colombo (Milan), Charles Richard Hutchinson (Cross Plains, WI), Sharee Otten (Madison, WI), Claudio Scotti (Motta Viscontio)
Primary Examiner: Karen Carlson
Law Firm: Nikaido Marmelstein Murray & Oram LLP
Application Number: 8/760,116